CXCR4+骨髓间充质干细胞在ox-LDL刺激下可向内皮细胞迁移.doc

CXCR4+BMSC迁移与Ox-LDL致内皮细胞损伤的研究 余刚1,2 夏红利2 李敏才1*作者单位：437100 咸宁， 作者单位：437100 咸宁，1湖北科技学院基础医学院, 2咸宁市中心医院胃肠外科（湖北科技学院附属医院） 通讯作者：李敏才Email：mincaili01@ 摘要：目的：基质细胞衍生因子1（SDF-1）是影响干/祖细胞迁移的关键趋化因子之一。然而干细胞如何迁移到病变部位的分子机制并不十分清楚。本实验旨在研究内皮细胞分泌的SDF-1是否影响CXCR4+干/祖细胞迁移与粘附功能。方法：首先从骨髓中分离出CXCR4+BMSC，然后用低密度脂蛋白（ox-LDL）刺激人内皮细胞诱导SDF-1α表达。结果：研究发现ox-LDL刺激内皮细胞可以引起SDF-1α表达升高；含SDF-1α培养基上清能促进CXCR4+BMSC的迁移，同时这种迁移可被CXCR4+抗体抑制。结论：我们的结果提示在致动脉粥样硬化（AS）病变过程中，BMSC可通过SDF-1α/CXCR4 轴向内皮细胞发生迁移运动。 关键词：BMSC ,CXCR4，ox-LDL，SDF-1α，迁移 The study of the migration of CXCR4 + MSC and the Ox-LDL induced injury in endothelial cell Abstract: Chemokine stromal cell-derived factor 1 (SDF-1α) is involved in the process of migration. We study whether the SDF-1αplays a role in migration of BM-derived CXCR4+(receptor for SDF- 1α) stem cells. Methods: HUVECs were cultured from human umbilical cords and was treated with ox-LDL. The mRNA and protein expression of SDF-1α was detected in HUVECs. CXCR4+BMSCs were isolated and tested by migration and adhesion assays. Results: Ox-LDL induced HUVECs to increase the mRNA and protein expression of SDF-1α. Ox-LDL increased the migratory response of CXCR4+BMSCs. When the neutralizing SDF-1α antibody abrogated the secreted SDF-1α, the migration response of CXCR4+BMSCs markedly decreased. Conclusions: Our data indicated that HUVECs stimulated by ox-LDL could increase the BMSCs migratory response via SDF-1α/CXCR4 signaling axis. These findings provide a new paradigm for biological effects of ox-LDL and have implications for novel stem cell therapeutic strategies for atherosclerosis. Key word：BMSC, CXCR4, ox-LDL，SDF-1α，Migratory 血管再生或重建是机体为适应环境因素刺激产生的生理或病理反应过程中一个关键的事件 ADDIN EN.CITE ADDIN EN.CITE.DATA [1]。干细胞参与了血管再生或血管损伤后修复：如机体缺血梗死区可吸引骨髓间充质干细胞（BMSC）并介导其迁移参与修复，提示可能与梗死区存在特异的趋化BMSC细胞因子有关 ADDIN EN.CITE ADDIN EN.CITE.DATA [2]。BMSC是如何迁移到受损血管的机制并不十分清楚。 细胞的迁移往往与细胞因子及其细胞因子受体有关 ADDIN EN.CITE ADDIN EN.CITE.DATA [3]。基质细胞衍生因子1（SDF-1α）是介导细胞迁移的常见趋化因子之一 ADDIN EN.CITE ADDIN EN.CITE.DATA [4]。SDF-1α与其受体CXC